Only 10% of glaucoma cases are caused by known genes. Now, researchers have discovered that glaucoma might not stem from single gene mutations, but two (or more) mutated genes working together, according to a study in the April 1 issue of Human Molecular Genetics.
Geneticists have long suspected a link between glaucoma and gene WDR36, but have been unable to figure out what the gene does and why some people with variations of the gene get glaucoma while others dont.
So, researchers used a yeast gene that is extremely similar to WDR36 but much easier to experiment with. Then they examined the functional consequences of mutated forms of the gene. Alone, no defects resulted. When combined with the disrupted gene STI1, however, nearly half of the tested variants showed modified levels of cell viability.
Our results suggest there have to be changes in several different genes in order for WDR36 to cause the disease, says lead researcher Michael Walter, Ph.D., chair of the Department of Medical Genetics and professor in the Department of Ophthalmology at the
Dr. Walters team also figured out the genes normal function. WDR36 plays a role in ribosome RNA (rRNA) creation. The researchers suspect that variations in the genetic sequence affect RNA production and, in turn, the cells ability to function.
Glaucoma happens when WDR36 isnt producing ribosomes properly and STI1 isnt packaging those proteins properly. You need at least these two mutations to cause the disease, Dr. Walter says.
STI1 is only one of many other genes in which mutations must take place in order for WDR36 to cause glaucoma, he adds.
The researchers hope that by further understanding the genetic causes of glaucoma, they might be able to find a way to prevent it. Glaucoma is one of the few blinding eye diseases that we can actually treat. But right now were only treating the symptoms, not the disease, Dr. Walter says. If we can understand why [patients] get glaucoma, then we have some important clues to use in developing second-generation medications that treat the disease itself.
Footz TK, Johnson JL, Dubois S, et al. Glaucoma-associated WDR36 variants encode functional defects in a yeast model system. Human Molecular Genetics 2009 Apr 1;18(7):1276-87.